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Open data
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Basic information
| Entry | Database: PDB / ID: 8ww2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Title | GPR3/Gs complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / GPCR-G-protein complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Function / homology | Function and homology informationsphingosine-1-phosphate receptor activity / regulation of meiotic nuclear division / regulation of metabolic process / G protein-coupled receptor activity / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor ...sphingosine-1-phosphate receptor activity / regulation of meiotic nuclear division / regulation of metabolic process / G protein-coupled receptor activity / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / positive regulation of cold-induced thermogenesis / retina development in camera-type eye / GTPase binding / Ca2+ pathway / fibroblast proliferation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / signal transduction / extracellular exosome / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Biological species | Homo sapiens (human)![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.79 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Authors | He, Y. / Xiong, Y. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Funding support | China, 1items
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Citation | Journal: Cell Res / Year: 2024Title: Identification of oleic acid as an endogenous ligand of GPR3. Authors: Yangjie Xiong / Zhenmei Xu / Xinzhi Li / Yuqin Wang / Jing Zhao / Na Wang / Yaning Duan / Ruixue Xia / Zhengbin Han / Yu Qian / Jiale Liang / Anqi Zhang / Changyou Guo / Asuka Inoue / Yu Xia ...Authors: Yangjie Xiong / Zhenmei Xu / Xinzhi Li / Yuqin Wang / Jing Zhao / Na Wang / Yaning Duan / Ruixue Xia / Zhengbin Han / Yu Qian / Jiale Liang / Anqi Zhang / Changyou Guo / Asuka Inoue / Yu Xia / Zheng Chen / Yuanzheng He / ![]() Abstract: Although GPR3 plays pivotal roles in both the nervous system and metabolic processes, such as cold-induced thermogenesis, its endogenous ligand remains elusive. Here, by combining structural approach ...Although GPR3 plays pivotal roles in both the nervous system and metabolic processes, such as cold-induced thermogenesis, its endogenous ligand remains elusive. Here, by combining structural approach (including cryo-electron microscopy), mass spectrometry analysis, and functional studies, we identify oleic acid (OA) as an endogenous ligand of GPR3. Our study reveals a hydrophobic tunnel within GPR3 that connects the extracellular side of the receptor to the middle of plasma membrane, enabling fatty acids to readily engage the receptor. Functional studies demonstrate that OA triggers downstream G signaling, whereas lysophospholipids fail to activate the receptor. Moreover, our research reveals that cold stimulation induces the secretion of OA in mice, subsequently activating G/cAMP/PKA signaling in brown adipose tissue. Notably, brown adipose tissues from Gpr3 knockout mice do not respond to OA during cold stimulation, reinforcing the significance of GPR3 in this process. Finally, we propose a "born to be activated and cold to enhance" model for GPR3 activation. Our study provides a starting framework for the understanding of GPR3 signaling in cold-stimulated thermogenesis. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| History |
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 8ww2.cif.gz | 193.8 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb8ww2.ent.gz | 145.8 KB | Display | PDB format |
| PDBx/mmJSON format | 8ww2.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 8ww2_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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| Full document | 8ww2_full_validation.pdf.gz | 1.2 MB | Display | |
| Data in XML | 8ww2_validation.xml.gz | 41.2 KB | Display | |
| Data in CIF | 8ww2_validation.cif.gz | 63.4 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ww/8ww2 ftp://data.pdbj.org/pub/pdb/validation_reports/ww/8ww2 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 37881MC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG
| #1: Protein | Mass: 44668.293 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: ![]() |
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| #2: Protein | Mass: 38059.629 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: ![]() |
| #3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Production host: ![]() |
-Antibody / Protein , 2 types, 2 molecules NR
| #4: Antibody | Mass: 15140.742 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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| #5: Protein | Mass: 35030.387 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GPR3 / Production host: ![]() |
-Non-polymers , 4 types, 5 molecules 






| #6: Chemical | ChemComp-OLA / |
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| #7: Chemical | ChemComp-Y01 / |
| #8: Chemical | ChemComp-PLM / |
| #9: Water | ChemComp-HOH / |
-Details
| Has ligand of interest | N |
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| Has protein modification | Y |
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: GPCR/G-protein complex / Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT |
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| Molecular weight | Experimental value: NO |
| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: ![]() |
| Buffer solution | pH: 7.5 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: FEI TITAN KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 1200 nm |
| Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
| EM software | Name: PHENIX / Category: model refinement | ||||||||||||||||||||||||
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| CTF correction | Type: NONE | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 2.79 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 288793 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refine LS restraints |
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About Yorodumi




Homo sapiens (human)

China, 1items
Citation

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gel filtration


